Preterm birth and infection: pathogenic possibilities.

Preterm delivery remains the preeminent problem in perinatal care worldwide. Recent data suggest that cervical/vaginal microflora, and/or the inflammatory responses they engender, produce factors which can cause or predispose to preterm labor and rupture of membranes. Microorganisms mediating such processes may not be "recognized pathogens" and are often considered normal flora. These microorganisms may act singly, additively, or synergistically with host factors released during an induced inflammatory response. Both qualitative and quantitative aspects of cervical/vaginal microflora are likely important. Multiple cervical/vaginal microorganisms produce IgA proteases, neuraminidases, and mucinases which may facilitate passage of these and other agents past cervical barriers and into the lower uterine segment. Multiple microflora also produce phospholipases A2 and C, each of which can locally augment production of eicosanoids within the uterus which are important in cervical ripening and labor. Similar microflora produce various proteases, including collagenase, which can focally weaken the amniochorion and predispose to premature rupture of membranes and cervical ripening. Intrauterine microorganisms induce inflammatory reaction and may engender local release of similar proteases, phospholipases, oxygen radicals, as well as platelet activating factor (PAF), and lymphokines which can also initiate or further potentiate labor-inducing mechanisms. Roles for uteroplacental or systemic release of tumor necrosis factor (TNF) and various interferons are beginning to be understood. Recognition of microbe-induced pathogenesis of some cases of preterm birth offers the hope of specific treatment and prophylaxis. In recent studies, administration of erythromycin and tocolytic agents was associated with an improved outcome in selected women. "Just why so many gravidas go into labor prematurely and hence give birth to infants who often are unable to cope with extrauterine conditions is one of the great unsolved problems of obstetrics."